Herbal medicine(HM)has been extensively researched and widely used since ancient times.Currently,as one of the emerging directions in HM modernization research,herbal medicine-derived nanovesicles(HMDNV),a type of nan...Herbal medicine(HM)has been extensively researched and widely used since ancient times.Currently,as one of the emerging directions in HM modernization research,herbal medicine-derived nanovesicles(HMDNV),a type of nanoparticle obtained from destructed plant tissues,hold considerable promise for disease treatment and drug delivery.The recent studies related to HMDNV and miRNAs are summarized in this review,with a special emphasis on their basic characteristics and biological activities,to provide ideas for future scientific research on HMDNV and enrich the content of active components of Traditional Chinese Medicine(TCM).展开更多
AIM:To investigate the preparation,physicochemical characterization and cytotoxicity in vitro of Gemcitabine-loaded poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-PDLLA) nanovesicles. METHODS:The nanovesicle carri...AIM:To investigate the preparation,physicochemical characterization and cytotoxicity in vitro of Gemcitabine-loaded poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-PDLLA) nanovesicles. METHODS:The nanovesicle carriers were prepared from the amphiphilic block copolymer of PEG-PDLLA by a double emulsion technique,and gemcitabine was used as the model drug. The morphology of the nanovesicles was determined by scanning and transmission electron microscopy,and the drug content,drug entrapment and drug-release curve in vitro were detected by UV-Vis-NIR spectrophotometry. Cytotoxicity in the human pancreatic cancer cell line SW1990 was tested by 3-(4,5-dimethyl) ethiazole (MTT) assay.RESULTS:The gemcitabine-loaded nanovesicles were hollow nanospheres with a mean size of 200.6 nm,drugloading of 4.14% and drug embedding ratio of 20.54%. The nanovesicles showed excellent controlled release that was characterized by a fast initial release during the first 72 h,followed by a slower and continuous release. The MTT assay demonstrated that gemcitabine-loaded nanovesicles exhibited dose-dependent and time-delayed cytotoxicity in the human pancreatic cancer cell line SW1990.CONCLUSION:Gemcitabine-loaded PEG-PDLLA nanovesicles prepared by a double emulsion technique exhibited good performance for controlled drug release,and had similar cytotoxic activity to free gem-citabine.展开更多
Drug resistance is accountable for the inadequate outcome of chemotherapy in clinics.The newly emerging role of nitric oxide(NO)to conquer drug resistance has been recognized as a potential strategy.However,it remains...Drug resistance is accountable for the inadequate outcome of chemotherapy in clinics.The newly emerging role of nitric oxide(NO)to conquer drug resistance has been recognized as a potential strategy.However,it remains a great challenge to realize targeted delivery as well as accurate release of NO at desired sites.Herein,we developed a PEGylated indocyanine green(m PEG-ICG)integrated nanovesicle system(PIDA)to simultaneously load doxorubicin hydrochloride(DOX·HCl)and the NO donor L-arginine(L-Arg),which can produce NO triggered by NIR light irradiation and exert multimodal therapy to sensitize drug-resistant cancers.Upon 808 nm irradiation,the NO released from PIDA led to a decrease in mitochondrial membrane potential,an increase in ROS and significant ATP depletion in K562/ADR cells,thus inhibiting cell growth and resolving the problem of drug resistance.Consequently,the in vivo experiment on K562/ADR-bearing nude mice indicated that PIDA nanovesicles achieved significant anticancer efficacy with a tumor inhibition rate of 80.8%.Above all,PIDA nanovesicles offer guidance for designing nanoplatforms for drug-resistant cancer treatment.展开更多
Lipidic nanovesicles (so called liposomes) were one the earliest forms of nanovectors. One of their limits was our lack of knowledge on the delivery pathway of their content to the target cell cytoplasm. The present c...Lipidic nanovesicles (so called liposomes) were one the earliest forms of nanovectors. One of their limits was our lack of knowledge on the delivery pathway of their content to the target cell cytoplasm. The present communication describes an efficient way to enhance the delivery. Pulsed electric fields (PEF) are known since the early 80’s to mediate a fusogenic state of plasma membranes when applied to a cell suspension or a tissue. Polykaryons are detected when PEF are applied on cells in contact during or after the pulses. Heterofusion can be obtained when a cell mixture is pulsed. When lipidic nanovesicles, either small unilamellar vesicles (SUVs) or large unilamellar vesicles (LUVs), are electrostatically brought in contact with electropermeabilized cells by a salt bridge, their content is delivered into the cytoplasm in electropermeabilized cells. The PEF parameters are selected to affect specifically the cells leaving the vesicles unaffected. It is the electropermeabilized state of the cell membrane that is the trigger of the merging between the plasma membrane and the lipid bilayer. The present investigation shows that the transfer of macromolecules can be obtained;i.e. 20 kD dextrans can be easily transferred while a direct transfer does not take place under the same electrical parameters. Cell viability was not affected by the treatment. As delivery is present only on electropermeabilized cells, a targeting of the effect is obtained in the volume where the PEF parameters are over the critical value for electropermeabilization. A homogeneous cytoplasm labeling is observed under digitised videomicroscopy. The process is a content and “membrane” mixing, following neither a kiss and run or an endocytotic pathway.展开更多
Squamous cell carcinoma (SCC) and melanoma are malignant human cancers of the skin with an annual mortality that exceeds 10,000 cases every year in the USA alone. In this study, the lysosomal protein saposin C (SapC) ...Squamous cell carcinoma (SCC) and melanoma are malignant human cancers of the skin with an annual mortality that exceeds 10,000 cases every year in the USA alone. In this study, the lysosomal protein saposin C (SapC) and the phospholipid dioloylphosphatidylserine (DOPS) were assembled into cancer-selective nanovesicles (SapC-DOPS) and successfully tested using several in vitro and in vivo skin cancer models. Using MTT assay that measures the percentage of cell death, SapC-DOPS cytotoxic effect on three skin tumor cell lines (squamous cell carcinoma, SK-MEL-28, and MeWo) was compared to two normal nontumorigenic skin cells lines, normal immortalized keratinocyte (NIK) and human fibroblast cell (HFC). We observed that the nanovesicles selectively killed the skin cancer cells by inducing apoptotic cell death whereas untransformed skin cancer cells remained unaffected. Using subcutaneous skin tumor xenografts, animals treated with SapC-DOPS by subcutaneous injection showed a 79.4% by volume tumor reduced compared to the control after 4 days of treatment. We observed that the nanovesicles killed skin cancer cells by inducing apoptotic cell death compared to the control as revealed by TUNEL staining of xenograft tumor sections.展开更多
Plant-derived nanovesicles(PDNVs)derived from natural green products have emerged as an attractive nanoplatform in biomedical application.They are usually characterized by unique structural and biological functions,su...Plant-derived nanovesicles(PDNVs)derived from natural green products have emerged as an attractive nanoplatform in biomedical application.They are usually characterized by unique structural and biological functions,such as the bioactive lipids/proteins/nucleic acids as therapeutics and targeting groups,immune-modulation,and long-term circulation.With the rapid development of nanotechnology,materials,and synthetic chemistry,PDNVs can be engineered with multiple functions for efficient drug delivery and specific killing of diseased cells,which represent an innovative biomaterial with high biocompatibility for fighting against cancer.In this review,we provide an overview of the state-of-theart studies concerning the development of PDNVs for cancer therapy.The original sources,methods for obtaining PDNVs,composition and structure are introduced systematically.With an emphasis on the featured application,the inherent anticancer properties of PDNVs as well as the strategies in constructing multifunctional PDNVs-based nanomaterials will be discussed in detail.Finally,some scientific issues and technical challenges of PDNVs as promising options in improving anticancer therapy will be discussed,which are expected to promote the further development of PDNVs in clinical translation.展开更多
As a high-risk trauma,deep burns are always hindered in their repair process by decreased tissue regeneration capacity and persistent infections.In this study,we developed a simultaneous strategy for deep burn wounds ...As a high-risk trauma,deep burns are always hindered in their repair process by decreased tissue regeneration capacity and persistent infections.In this study,we developed a simultaneous strategy for deep burn wounds treatment using functional nanovesicles with antibacterial and tissue remodeling properties,delivered via a click-chemistry hydrogel.An aggregation-induced emission photosensitizer of 4-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1-(2-hydroxyethyl)pyridin-1-ium bromide(THB)with excellent photodynamic properties was first prepared,and then combined with readily accessible adipose stem cells-derived nanovesicles to generate the THB functionalized nanovesicles(THB@ANVs).The THB@ANVs showed strong antibacterial activity against Gram-positive bacteria(up to 100%killing rate),and also beneficial effects on tissue remodeling,including promoting cell migration,cell proliferation,and regulating immunity.In addition,we prepared a click-hydrogel of carboxymethyl chitosan for effective delivery of THB@ANVs on wounds.This hydrogel could be injected to conform to the wound morphology while responding to the acidic microenvironment.In vivo evaluations of wound healing revealed that the THB@ANVs hydrogel dressing efficiently accelerated the healing of second-degree burn wounds by reducing bacterial growth,regulating inflammation,promoting early angiogenesis,and collagen deposition.This study provides a promising candidate of wound dressing with diverse functions for deep burn wound repair.展开更多
Cellular nanovesicles which are referred to as cell-derived,nanosized lipid bilayer structures,have emerged as a promising platform for regulating immune responses.Owing to their outstanding advantages such as high bi...Cellular nanovesicles which are referred to as cell-derived,nanosized lipid bilayer structures,have emerged as a promising platform for regulating immune responses.Owing to their outstanding advantages such as high biocompatibility,prominent structural stability,and high loading capacity,cellular nanovesicles are suitable for delivering various immunomodulatory molecules,such as small molecules,nucleic acids,peptides,and proteins.Immunomodulation induced by cellular nanovesicles has been exploited to modulate immune cell behaviors,which is considered as a novel cell-free immunotherapeutic strategy for the prevention and treatment of diverse diseases.Here we review emerging concepts and new advances in leveraging cellular nanovesicles to activate or suppress immune responses,with the aim to explicate their applications for immunomodulation.We overview the general considerations and principles for the design of engineered cellular nanovesicles with tailored immunomodulatory activities.We also discuss new advances in engineering cellular nanovesicles as immunotherapies for treating major diseases.展开更多
Background:Immunosuppressive M2 macrophages in the tumor microenvironment(TME)can mediate the therapeutic resistance of tumors,and seriously affect the clinical efficacy and prognosis of tumor patients.This study aims...Background:Immunosuppressive M2 macrophages in the tumor microenvironment(TME)can mediate the therapeutic resistance of tumors,and seriously affect the clinical efficacy and prognosis of tumor patients.This study aims to develop a novel drug delivery system for dual-targeting tumor and macrophages to inhibit tumor and induce macrophage polarization.Methods:The anti-tumor effects of methyltransferase like 14(METTL14)were investigated both in vitro and in vivo.The underlying mechanisms of METTL14 regulating macrophages were also explored in this study.We further constructed the cyclic(Arg-Gly-Asp)(cRGD)peptide modified macrophage membrane-coated nanovesicles to co-deliver METTL14 and the TLR4 agonist.Results:We found that METTL14 significantly inhibits the growth of tumor in vitro.METTL14 might downregulate TICAM2 and inhibit the Toll-like receptor 4(TLR4)pathway of macrophages,meanwhile,the combination of METTL14 and the TLR4 agonist could induce M1 polarization of macrophages.Macrophage membrane-coated nanovesicles are characterized by easy modification,drug loading,and dual-targeting tumor and macrophages,and cRGD modification can further enhance its targeting ability.It showed that the nanovesicles could improve the in vivo stability of METTL14,and dual-target tumor and macrophages to inhibit tumor and induce M1 polarization of macrophages.Conclusions:This study anticipates achieving the dual purposes of tumor inhibition and macrophage polarization,and providing a new therapeutic strategy for tumors.展开更多
Immune checkpoint inhibitors(ICIs)have revolutionized cancer treatment for their unprecedented clinical efficacy.Signal regulatory proteinα(SIRPα)is a phagocytic checkpoint expressed on macrophages,dendritic cells,o...Immune checkpoint inhibitors(ICIs)have revolutionized cancer treatment for their unprecedented clinical efficacy.Signal regulatory proteinα(SIRPα)is a phagocytic checkpoint expressed on macrophages,dendritic cells,other myeloid cells.Cancer cells inhibit macrophage phagocytosis through the interaction of the CD47-SIRPαaxis.Disrupting the CD47-SIRPαaxis has therefore been a promising strategy in restoring the immune attack against cancer.Herein,we engineered cellular membrane nanovesicles(NVs)presenting SIRPαreceptors for phagocytosis checkpoint blockade to augment the antitumor immune response.Furthermore,zebularine(Zeb),an inhibitor of DNA methyltransferase,was encapsulated into SIRPαNVs to reprogram the immunosuppressive tumor microenvironment together with blockade of phagocytosis checkpoint.It is demonstrated that SIRPα@Zeb can improve tumor immunogenicity,the polarization of tumor-associated macrophages to the M1 phenotype,increase the infiltration of CD8^(+)T lymphocytes in tumors.The robust antitumor immune response induced by SIRPα@Zeb significantly suppressed tumor growth and extended mice-bearing melanoma xenograft survival.展开更多
Extracellular vesicles(EVs)are phospholipid bilayer vesicles actively secreted by cells,that contain a variety of functional nucleic acids,proteins,and lipids,and are important mediums of intercellular communication.B...Extracellular vesicles(EVs)are phospholipid bilayer vesicles actively secreted by cells,that contain a variety of functional nucleic acids,proteins,and lipids,and are important mediums of intercellular communication.Based on their natural properties,EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers.Among them,plant-derived nanovesicles(PNVs)are characterized as natural disease therapeutics with many advantages such as simplicity,safety,eco-friendliness,low cost,and low toxicity due to their abundant resources,large yield,and low risk of immunogenicity in vivo.This review systematically introduces the biogenesis,isolation methods,physical characterization,and components of PNVs,and describes their administration and cellular uptake as therapeutic agents.We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers,including anti-inflammatory,anticancer,wound healing,regeneration,and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19.Finally,the toxicity and immunogenicity,the current clinical application,and the possible challenges in the future development of PNVs were analyzed.We expect the functions of PNVs to be further explored to promote clinical translation,thereby facilitating the development of a new framework for the treatment of human diseases.展开更多
Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers.Recently,extracellular vesicles(EVs),natur...Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers.Recently,extracellular vesicles(EVs),naturally cell-secreted lipid membrane-bound vesicles laden with biological cargos including proteins,lipids,and nucleic acids,have drawn wide attention due to their ability to promote wound healing and tissue regeneration.However,current exploitation of EVs as therapeutic agents is limited by their low isolation yields and tedious isolation processes.To circumvent these challenges,bioinspired cell-derived nanovesicles(CDNs)that mimic EVs were obtained by shearing mesenchymal stem cells(MSCs)through membranes with different pore sizes.Physical characterisations and highthroughput proteomics confirmed that MSC-CDNs mimicked MSC-EVs.Moreover,these MSC-CDNs were efficiently uptaken by human dermal fibroblasts and demonstrated a dose-dependent activation of MAPK signalling pathway,resulting in enhancement of cell proliferation,cell migration,secretion of growth factors and extracellular matrix proteins,which all promoted tissue regeneration.Of note,MSC-CDNs enhanced angiogenesis in human dermal microvascular endothelial cells in a 3D PEGfibrin scaffold and animal model,accelerating wound healing in vitro and in vivo.These findings suggest that MSC-CDNs could replace both whole cells and EVs in promoting wound healing and tissue regeneration.展开更多
Extracellular vesicles(EVs)generated from mesenchymal stem cells(MSCs)play an essential role in modulating cell–cell communication and tissue regeneration.The clinical translation of EVs is constrained by the poor yi...Extracellular vesicles(EVs)generated from mesenchymal stem cells(MSCs)play an essential role in modulating cell–cell communication and tissue regeneration.The clinical translation of EVs is constrained by the poor yield of EVs.Extrusion has recently become an effective technique for producing a large scale of nanovesicles(NVs).In this study,we systematically compared MSC NVs(from extrusion)and EVs(from natural secretion).Proteomics and RNA sequencing data revealed that NVs resemble MSCs more closely than EVs.Additionally,microRNAs in NVs are related to cardiac repair,fibrosis repression,angiogenesis.Lastly,intravenous delivery of MSC NVs improved heart repair and cardiac function in a mouse model of myocardial infarction.展开更多
The lung is one of the most common sites for cancer metastasis.Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells.Therefore,down-regula...The lung is one of the most common sites for cancer metastasis.Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells.Therefore,down-regulating the production of collagens may contribute to the inhibition of lung metastasis.It has been suggested that mi R-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens.Indeed,our clinical lung tumor data shows that mi R-29 a-3 p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients’outcomes.However,suitable carriers need to be selected to deliver this therapeutic mi RNA to the lungs.In this study,we found that the chemotherapy drug cisplatin facilitated mi R-29 a-3 p accumulation in the exosomes of lung tumor cells,and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation.To scale up the preparation and simplify the delivery system,we designed a lung-targeting liposomal nanovesicle(by adjusting the molar ratio of DOTAP/cholesterol-mi RNAs to 4:1)to carry mi R-29 a-3 p and mimic the exosomes.This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo,thus alleviating the establishment of a pro-metastatic environment for circulating lung tumor cells.展开更多
There are extensive studies on the applications of extracellular vesicles(EVs)produced in cell culture for therapeutic drug development.However,large quantities of EVs are needed for in vivo applications,which require...There are extensive studies on the applications of extracellular vesicles(EVs)produced in cell culture for therapeutic drug development.However,large quantities of EVs are needed for in vivo applications,which requires high production costs and time.Thus,the development of new EV sources is essential to facilitate their use.Accordingly,plant-derived exosome-like nanovesicles are an emerging alternative for culture-derived EVs.Until now,however,few studies have explored their biological functions and uses.Therefore,it is necessary to elucidate biological activities of plant-derived exosome-like nanovesicles and harness vesicles for biomedical applications.Herein,cabbage and red cabbage were used as nanovesicle sources owing to their easy cultivation.First,an efficient method for nanovesicle isolation from cabbage(Cabex)and red cabbage(Rabex)was developed.Furthermore,isolated nanovesicles were characterized,and their biological functions were assessed.Both Cabex and Rabex promoted mammalian cell proliferation and,interestingly,suppressed inflammation in immune cells and apoptosis in human keratinocytes and fibroblasts.Finally,therapeutic drugs were encapsulated in Cabex or Rabex and successfully delivered to human cells,demonstrating the potential of these vesicles as alternative drug delivery vehicles.Overall,the current results provide strong evidence for the wide application of Cabex and Rabex as novel therapeutic biomaterials.展开更多
Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death.Nanoparticle-mediated multidrug combination treatment has been proven to be a feas...Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death.Nanoparticle-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these challenges.In the present study,amphipathic block polymer of methoxyl poly(ethylene glycol)-poly(aspartyl(dibutylethylenediamine)-co-phenylalanine)(m PEG-P(Asp(DBA)-co-Phe))was synthesized and self-assembled into p H-responsive polymeric vesicle.The vesicle was utilized to co-deliver cancer-associated epidermal growth factor(EGFR)inhibitor of afatinib and DNA-damaging chemotherapeutic doxorubicin hydrochloride(DOX)for enhanced non-small-cell lung cancer(NSCLC)therapy.As evaluated in vitro,the p H-responsive design of nanovesicle resulted in a rapid release of encapsulated drugs into tumor cells and caused enhanced cell apoptosis.In addition,in vivo therapeutic studies were conducted and the results evidenced that the co-delevery of DOX and afatinib using p H-sensitive nanovector was a promising strategy for NSCLC treatment.展开更多
Translation of exosome-based therapies to pharmaceutical use is hindered by difficulties in large-scale and cost-effective production of clinical-grade exosomes.The rational design of nanovesicles that mimic the funct...Translation of exosome-based therapies to pharmaceutical use is hindered by difficulties in large-scale and cost-effective production of clinical-grade exosomes.The rational design of nanovesicles that mimic the functionalities and physicochemical properties of exosomes may circumvent these issues.In this study,membranes and secretome from efficacy-potentiated mesenchymal stem cells(MSCs)were developed into size-controllable nanovesicles(Meseomes).MSCs were primed with interferon-y(IFNy)and tumor necrosis factor-a(TNFa),harvested,and exosome-mimicking Meseomes were subsequently synthesized via one-step extrusion.Meseomes demonstrated significant enhancement of pro-angiogenic,pro-proliferative,antiinflammatory,and anti-fibrotic effects on endothelial cells,macrophages,and hepatic stellate cells in vitro.Meseomes from primed MSCs benefited from an enrichment of bioactive and therapeutic molecules compared to nanovesicles from unprimed MSCs,as validated by liquid chromatography-mass spectrometry(LC-MS)proteomic analysis.Systemic administration of Meseomes to acute liver injury models resulted in the recovery of liver function,attenuated tissue necrosis.Further assessment of locally administered Meseomes in acute hindlimb ischemia models resulted in the salvage of the majority of the ischemic hindlimb(>80%),which was due to enhanced angiogenesis and M2 macrophage polarization.The versatility and therapeutic efficacy of our developed acellular Meseomes offer an appealing alternative to traditional cell or exosome therapies for regenerative and translational medicine.展开更多
Oligonucleotide therapeutics have great potential to target the currently undruggable genes and to generate entirely new therapeutic paradigms in multiple types of disease,thus having attracted much attention in recen...Oligonucleotide therapeutics have great potential to target the currently undruggable genes and to generate entirely new therapeutic paradigms in multiple types of disease,thus having attracted much attention in recent years.However,their applications are greatly hindered by a lack of safe and efficient oligonucleotide-delivery vectors.Polyplex nanovesicles formed from oligonucleotides and the cationic block have shown exceptional features for the delivery of therapeutic oligonucleotides and other biopharmaceuticals.Nevertheless,these polyplex nanovesicles are deeply fraught with difficulty in tolerating physiological ionic strength.Inspired by the high binding ability between the dipicolylamine(DPA)/zinc(Ⅱ)complex and the phosphodiester moieties of oligonucleotides,herein,we designed a coordinative cationic block to solve the intrinsic stability dilemma.Moreover,we found the stability of the resulted polyplex nanovesicles could be easily tuned by the content of coordinated zinc ions.In vitro cellular studies implied that the prepared zinc(Ⅱ)-coordinative polyplex nanovesicles preferred to retain in the lysosomes upon internalization,making them ideal delivery candidates for the lysosome-targeting oligonucleotide therapeutics.展开更多
Gold nanovesicles(GVs) with unique plasmonic property and large cavity hold great potential as a stimuli-responsive nanocarrier to deliver drugs for efficient tumor chemotherapy and other therapies synergistically.Her...Gold nanovesicles(GVs) with unique plasmonic property and large cavity hold great potential as a stimuli-responsive nanocarrier to deliver drugs for efficient tumor chemotherapy and other therapies synergistically.Herein,we developed doxorubicin-loaded gold nanovesicles(DGVs),offering infrared thermal(IRT) and photoacoustic(PA) dual-modal imaging guided mild hype rthermia-enhanced chemophotothermal cancer synergistic therapy.The DGVs are self-assembled by gold nanoparticles modified with amphiphilic copolymer in a predetermined concentration of doxorubicin through film rehydration method.Under the influence of laser excitation,the as-prepared DGVs exhibited good photothermal effect,which triggered the structural disruption of GVs and thus,allowed the efficient release of encapsulated DOX to enhance cell uptake for fluorescence imaging and tumor chemotherapy,respectively.In addition,DGVs also showed a strong PA and IRT signals in vivo.Our study demonstrated the potential of DGVs as stimuli-responsive drug delivery systems and cancer theranostics.展开更多
Extracellular vesicles are nano-to micro-scale,membrane-bound particles released by cells into extracellular space,and act as carriers of biomarkers and therapeutics,holding promising potential in translational medici...Extracellular vesicles are nano-to micro-scale,membrane-bound particles released by cells into extracellular space,and act as carriers of biomarkers and therapeutics,holding promising potential in translational medicine.However,the challenges remain in handling and detecting extracellular vesicles for disease diagnosis as well as exploring their therapeutic capability for disease treatment.Here,we review the recent engineering and technology advances by leveraging the power of sound waves to address the challenges in diagnostic and therapeutic applications of extracellular vesicles and biomimetic nanovesicles.We first introduce the fundamental principles of sound waves for understanding different acoustic-assisted extracellular vesicle technologies.We discuss the acoustic-assisted diagnostic methods including the purification,manipulation,biosensing,and bioimaging of extracellular vesicles.Then,we summarize the recent advances in acoustically enhanced therapeutics using extracellular vesicles and biomimetic nanovesicles.Finally,we provide perspectives into current challenges and future clinical applications of the promising extracellular vesicles and biomimetic nanovesicles powered by sound.展开更多
基金supported by the Tianjin Committee of Science and Technology of China(No.21ZYJDJC00080 and No.22ZYJDSS00040).
文摘Herbal medicine(HM)has been extensively researched and widely used since ancient times.Currently,as one of the emerging directions in HM modernization research,herbal medicine-derived nanovesicles(HMDNV),a type of nanoparticle obtained from destructed plant tissues,hold considerable promise for disease treatment and drug delivery.The recent studies related to HMDNV and miRNAs are summarized in this review,with a special emphasis on their basic characteristics and biological activities,to provide ideas for future scientific research on HMDNV and enrich the content of active components of Traditional Chinese Medicine(TCM).
文摘AIM:To investigate the preparation,physicochemical characterization and cytotoxicity in vitro of Gemcitabine-loaded poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-PDLLA) nanovesicles. METHODS:The nanovesicle carriers were prepared from the amphiphilic block copolymer of PEG-PDLLA by a double emulsion technique,and gemcitabine was used as the model drug. The morphology of the nanovesicles was determined by scanning and transmission electron microscopy,and the drug content,drug entrapment and drug-release curve in vitro were detected by UV-Vis-NIR spectrophotometry. Cytotoxicity in the human pancreatic cancer cell line SW1990 was tested by 3-(4,5-dimethyl) ethiazole (MTT) assay.RESULTS:The gemcitabine-loaded nanovesicles were hollow nanospheres with a mean size of 200.6 nm,drugloading of 4.14% and drug embedding ratio of 20.54%. The nanovesicles showed excellent controlled release that was characterized by a fast initial release during the first 72 h,followed by a slower and continuous release. The MTT assay demonstrated that gemcitabine-loaded nanovesicles exhibited dose-dependent and time-delayed cytotoxicity in the human pancreatic cancer cell line SW1990.CONCLUSION:Gemcitabine-loaded PEG-PDLLA nanovesicles prepared by a double emulsion technique exhibited good performance for controlled drug release,and had similar cytotoxic activity to free gem-citabine.
基金financially supported by the National Natural Science Foundation of China(81673384)。
文摘Drug resistance is accountable for the inadequate outcome of chemotherapy in clinics.The newly emerging role of nitric oxide(NO)to conquer drug resistance has been recognized as a potential strategy.However,it remains a great challenge to realize targeted delivery as well as accurate release of NO at desired sites.Herein,we developed a PEGylated indocyanine green(m PEG-ICG)integrated nanovesicle system(PIDA)to simultaneously load doxorubicin hydrochloride(DOX·HCl)and the NO donor L-arginine(L-Arg),which can produce NO triggered by NIR light irradiation and exert multimodal therapy to sensitize drug-resistant cancers.Upon 808 nm irradiation,the NO released from PIDA led to a decrease in mitochondrial membrane potential,an increase in ROS and significant ATP depletion in K562/ADR cells,thus inhibiting cell growth and resolving the problem of drug resistance.Consequently,the in vivo experiment on K562/ADR-bearing nude mice indicated that PIDA nanovesicles achieved significant anticancer efficacy with a tumor inhibition rate of 80.8%.Above all,PIDA nanovesicles offer guidance for designing nanoplatforms for drug-resistant cancer treatment.
文摘Lipidic nanovesicles (so called liposomes) were one the earliest forms of nanovectors. One of their limits was our lack of knowledge on the delivery pathway of their content to the target cell cytoplasm. The present communication describes an efficient way to enhance the delivery. Pulsed electric fields (PEF) are known since the early 80’s to mediate a fusogenic state of plasma membranes when applied to a cell suspension or a tissue. Polykaryons are detected when PEF are applied on cells in contact during or after the pulses. Heterofusion can be obtained when a cell mixture is pulsed. When lipidic nanovesicles, either small unilamellar vesicles (SUVs) or large unilamellar vesicles (LUVs), are electrostatically brought in contact with electropermeabilized cells by a salt bridge, their content is delivered into the cytoplasm in electropermeabilized cells. The PEF parameters are selected to affect specifically the cells leaving the vesicles unaffected. It is the electropermeabilized state of the cell membrane that is the trigger of the merging between the plasma membrane and the lipid bilayer. The present investigation shows that the transfer of macromolecules can be obtained;i.e. 20 kD dextrans can be easily transferred while a direct transfer does not take place under the same electrical parameters. Cell viability was not affected by the treatment. As delivery is present only on electropermeabilized cells, a targeting of the effect is obtained in the volume where the PEF parameters are over the critical value for electropermeabilization. A homogeneous cytoplasm labeling is observed under digitised videomicroscopy. The process is a content and “membrane” mixing, following neither a kiss and run or an endocytotic pathway.
文摘Squamous cell carcinoma (SCC) and melanoma are malignant human cancers of the skin with an annual mortality that exceeds 10,000 cases every year in the USA alone. In this study, the lysosomal protein saposin C (SapC) and the phospholipid dioloylphosphatidylserine (DOPS) were assembled into cancer-selective nanovesicles (SapC-DOPS) and successfully tested using several in vitro and in vivo skin cancer models. Using MTT assay that measures the percentage of cell death, SapC-DOPS cytotoxic effect on three skin tumor cell lines (squamous cell carcinoma, SK-MEL-28, and MeWo) was compared to two normal nontumorigenic skin cells lines, normal immortalized keratinocyte (NIK) and human fibroblast cell (HFC). We observed that the nanovesicles selectively killed the skin cancer cells by inducing apoptotic cell death whereas untransformed skin cancer cells remained unaffected. Using subcutaneous skin tumor xenografts, animals treated with SapC-DOPS by subcutaneous injection showed a 79.4% by volume tumor reduced compared to the control after 4 days of treatment. We observed that the nanovesicles killed skin cancer cells by inducing apoptotic cell death compared to the control as revealed by TUNEL staining of xenograft tumor sections.
基金This work was supported by the National Natural Science Foundation of China(Nos.81972547 and 82273306)the Hubei Province health and family planning scientific research project(WJ2023Q011,China).
文摘Plant-derived nanovesicles(PDNVs)derived from natural green products have emerged as an attractive nanoplatform in biomedical application.They are usually characterized by unique structural and biological functions,such as the bioactive lipids/proteins/nucleic acids as therapeutics and targeting groups,immune-modulation,and long-term circulation.With the rapid development of nanotechnology,materials,and synthetic chemistry,PDNVs can be engineered with multiple functions for efficient drug delivery and specific killing of diseased cells,which represent an innovative biomaterial with high biocompatibility for fighting against cancer.In this review,we provide an overview of the state-of-theart studies concerning the development of PDNVs for cancer therapy.The original sources,methods for obtaining PDNVs,composition and structure are introduced systematically.With an emphasis on the featured application,the inherent anticancer properties of PDNVs as well as the strategies in constructing multifunctional PDNVs-based nanomaterials will be discussed in detail.Finally,some scientific issues and technical challenges of PDNVs as promising options in improving anticancer therapy will be discussed,which are expected to promote the further development of PDNVs in clinical translation.
基金National Natural Science Foundation of China,Grant/Award Numbers:82102256,82272276,81972019,82102444,88241059,82272281Basic and Applied Basic Research Foundation of Guangdong Province,Grant/Award Numbers:2023A1515012375,2021B1515120036,2021A1515011453,2022A1515012160,2021A1515010949+3 种基金Chinese Postdoctoral Science Foundation,Grant/Award Number:2021M693638Excellent Young Researchers Program of the 5th Affiliated Hospital of SYSU,Grant/Award Number:WYYXQN-2021008National Key Research and Development Program of China,Grant/Award Number:2021YFC2302200Natural Science Fund of Guangdong Province for Distinguished Young。
文摘As a high-risk trauma,deep burns are always hindered in their repair process by decreased tissue regeneration capacity and persistent infections.In this study,we developed a simultaneous strategy for deep burn wounds treatment using functional nanovesicles with antibacterial and tissue remodeling properties,delivered via a click-chemistry hydrogel.An aggregation-induced emission photosensitizer of 4-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1-(2-hydroxyethyl)pyridin-1-ium bromide(THB)with excellent photodynamic properties was first prepared,and then combined with readily accessible adipose stem cells-derived nanovesicles to generate the THB functionalized nanovesicles(THB@ANVs).The THB@ANVs showed strong antibacterial activity against Gram-positive bacteria(up to 100%killing rate),and also beneficial effects on tissue remodeling,including promoting cell migration,cell proliferation,and regulating immunity.In addition,we prepared a click-hydrogel of carboxymethyl chitosan for effective delivery of THB@ANVs on wounds.This hydrogel could be injected to conform to the wound morphology while responding to the acidic microenvironment.In vivo evaluations of wound healing revealed that the THB@ANVs hydrogel dressing efficiently accelerated the healing of second-degree burn wounds by reducing bacterial growth,regulating inflammation,promoting early angiogenesis,and collagen deposition.This study provides a promising candidate of wound dressing with diverse functions for deep burn wound repair.
基金support from the College of Pharmacy at University of Illinois Chicago。
文摘Cellular nanovesicles which are referred to as cell-derived,nanosized lipid bilayer structures,have emerged as a promising platform for regulating immune responses.Owing to their outstanding advantages such as high biocompatibility,prominent structural stability,and high loading capacity,cellular nanovesicles are suitable for delivering various immunomodulatory molecules,such as small molecules,nucleic acids,peptides,and proteins.Immunomodulation induced by cellular nanovesicles has been exploited to modulate immune cell behaviors,which is considered as a novel cell-free immunotherapeutic strategy for the prevention and treatment of diverse diseases.Here we review emerging concepts and new advances in leveraging cellular nanovesicles to activate or suppress immune responses,with the aim to explicate their applications for immunomodulation.We overview the general considerations and principles for the design of engineered cellular nanovesicles with tailored immunomodulatory activities.We also discuss new advances in engineering cellular nanovesicles as immunotherapies for treating major diseases.
基金This study is supported by the National Natural Science Foundation of China(No.82203059)the China Postdoctoral Science Foundation(2021M701335).
文摘Background:Immunosuppressive M2 macrophages in the tumor microenvironment(TME)can mediate the therapeutic resistance of tumors,and seriously affect the clinical efficacy and prognosis of tumor patients.This study aims to develop a novel drug delivery system for dual-targeting tumor and macrophages to inhibit tumor and induce macrophage polarization.Methods:The anti-tumor effects of methyltransferase like 14(METTL14)were investigated both in vitro and in vivo.The underlying mechanisms of METTL14 regulating macrophages were also explored in this study.We further constructed the cyclic(Arg-Gly-Asp)(cRGD)peptide modified macrophage membrane-coated nanovesicles to co-deliver METTL14 and the TLR4 agonist.Results:We found that METTL14 significantly inhibits the growth of tumor in vitro.METTL14 might downregulate TICAM2 and inhibit the Toll-like receptor 4(TLR4)pathway of macrophages,meanwhile,the combination of METTL14 and the TLR4 agonist could induce M1 polarization of macrophages.Macrophage membrane-coated nanovesicles are characterized by easy modification,drug loading,and dual-targeting tumor and macrophages,and cRGD modification can further enhance its targeting ability.It showed that the nanovesicles could improve the in vivo stability of METTL14,and dual-target tumor and macrophages to inhibit tumor and induce M1 polarization of macrophages.Conclusions:This study anticipates achieving the dual purposes of tumor inhibition and macrophage polarization,and providing a new therapeutic strategy for tumors.
基金National Key R&D Program of China(No.2021YFA0909900)Zhejiang Provincial Natural Science Foundation of China(No.LY23C100001)+2 种基金National Natural Science Foundation of China(Nos.51973214 and 51503003)Kunpeng Program from Zhejiang Province,Zhejiang University's start-up packages,Fundamental Research Funds for the Central Universities(No.2021FZZX001-46)the Starry Night Science Fund at Shanghai Institute for Advanced Study of Zhejiang University(No.SN-ZJU-SIAS-009).
文摘Immune checkpoint inhibitors(ICIs)have revolutionized cancer treatment for their unprecedented clinical efficacy.Signal regulatory proteinα(SIRPα)is a phagocytic checkpoint expressed on macrophages,dendritic cells,other myeloid cells.Cancer cells inhibit macrophage phagocytosis through the interaction of the CD47-SIRPαaxis.Disrupting the CD47-SIRPαaxis has therefore been a promising strategy in restoring the immune attack against cancer.Herein,we engineered cellular membrane nanovesicles(NVs)presenting SIRPαreceptors for phagocytosis checkpoint blockade to augment the antitumor immune response.Furthermore,zebularine(Zeb),an inhibitor of DNA methyltransferase,was encapsulated into SIRPαNVs to reprogram the immunosuppressive tumor microenvironment together with blockade of phagocytosis checkpoint.It is demonstrated that SIRPα@Zeb can improve tumor immunogenicity,the polarization of tumor-associated macrophages to the M1 phenotype,increase the infiltration of CD8^(+)T lymphocytes in tumors.The robust antitumor immune response induced by SIRPα@Zeb significantly suppressed tumor growth and extended mice-bearing melanoma xenograft survival.
基金supported by National Natural Science Foundation of China(82274103,82074272,China)Program of Shanghai Academic Research Leader(21XD1403400,China)+1 种基金the Science and Technology Commission of Shanghai Municipality(20S21900300,China)Shanghai Sailing Program(20YF1412100,China)。
文摘Extracellular vesicles(EVs)are phospholipid bilayer vesicles actively secreted by cells,that contain a variety of functional nucleic acids,proteins,and lipids,and are important mediums of intercellular communication.Based on their natural properties,EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers.Among them,plant-derived nanovesicles(PNVs)are characterized as natural disease therapeutics with many advantages such as simplicity,safety,eco-friendliness,low cost,and low toxicity due to their abundant resources,large yield,and low risk of immunogenicity in vivo.This review systematically introduces the biogenesis,isolation methods,physical characterization,and components of PNVs,and describes their administration and cellular uptake as therapeutic agents.We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers,including anti-inflammatory,anticancer,wound healing,regeneration,and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19.Finally,the toxicity and immunogenicity,the current clinical application,and the possible challenges in the future development of PNVs were analyzed.We expect the functions of PNVs to be further explored to promote clinical translation,thereby facilitating the development of a new framework for the treatment of human diseases.
基金the National University of Singapore(Nano Nash Program A-0004336-00-00&A-000850400-00,Singapore)Nanyang Technological University,Singapore(grant number 001487-00001)+4 种基金the Industry Alignment Fund—Pre-Positioning(IAF-PP)grant(A20G1a0046 and R-148-000-307-305/A0004345-00-00)the Singapore Ministry of Education,under its Singapore Ministry of Education Academic Research Fund Tier 1(10051-MOE AcRF Tier 1:Thematic Call 2020)from Bertrand Czarnythe National University of Singapore Nano-NASH Program(NUHSRO/2020/002/Nano Nash/LOA)the National University of Singapore Yong Loo Lin School of Medicine Nanomedicine Translational Research Program(NUHSRO/2021/034/TRP/09/Nanomedicine)the financial supports from Agency for Science,Technology,and Research(A~*STAR,Singapore)Advanced Manufacturing and Engineering Individual Research Grant(AME IRG)(Project ID:A1883c0013,Singapore)。
文摘Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers.Recently,extracellular vesicles(EVs),naturally cell-secreted lipid membrane-bound vesicles laden with biological cargos including proteins,lipids,and nucleic acids,have drawn wide attention due to their ability to promote wound healing and tissue regeneration.However,current exploitation of EVs as therapeutic agents is limited by their low isolation yields and tedious isolation processes.To circumvent these challenges,bioinspired cell-derived nanovesicles(CDNs)that mimic EVs were obtained by shearing mesenchymal stem cells(MSCs)through membranes with different pore sizes.Physical characterisations and highthroughput proteomics confirmed that MSC-CDNs mimicked MSC-EVs.Moreover,these MSC-CDNs were efficiently uptaken by human dermal fibroblasts and demonstrated a dose-dependent activation of MAPK signalling pathway,resulting in enhancement of cell proliferation,cell migration,secretion of growth factors and extracellular matrix proteins,which all promoted tissue regeneration.Of note,MSC-CDNs enhanced angiogenesis in human dermal microvascular endothelial cells in a 3D PEGfibrin scaffold and animal model,accelerating wound healing in vitro and in vivo.These findings suggest that MSC-CDNs could replace both whole cells and EVs in promoting wound healing and tissue regeneration.
基金NC State University,the National Natural Science Foundation of China(No.82200276)the Grant of Key Research and Development Program of Hebei Province(No.203777117D)+1 种基金the Key Project of Hebei Provincial Health Commission(Nos.20201159 and 20180224)the Natural Science Foundation of Hebei Province(Nos.H2021206399 and H2022206295)。
文摘Extracellular vesicles(EVs)generated from mesenchymal stem cells(MSCs)play an essential role in modulating cell–cell communication and tissue regeneration.The clinical translation of EVs is constrained by the poor yield of EVs.Extrusion has recently become an effective technique for producing a large scale of nanovesicles(NVs).In this study,we systematically compared MSC NVs(from extrusion)and EVs(from natural secretion).Proteomics and RNA sequencing data revealed that NVs resemble MSCs more closely than EVs.Additionally,microRNAs in NVs are related to cardiac repair,fibrosis repression,angiogenesis.Lastly,intravenous delivery of MSC NVs improved heart repair and cardiac function in a mouse model of myocardial infarction.
基金supported by the National Natural Science Foundation of China(Grant Nos.81630068,31670881,and 81901466)China Postdoctoral Science Foundation(Grant No.2020TQ0282)。
文摘The lung is one of the most common sites for cancer metastasis.Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells.Therefore,down-regulating the production of collagens may contribute to the inhibition of lung metastasis.It has been suggested that mi R-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens.Indeed,our clinical lung tumor data shows that mi R-29 a-3 p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients’outcomes.However,suitable carriers need to be selected to deliver this therapeutic mi RNA to the lungs.In this study,we found that the chemotherapy drug cisplatin facilitated mi R-29 a-3 p accumulation in the exosomes of lung tumor cells,and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation.To scale up the preparation and simplify the delivery system,we designed a lung-targeting liposomal nanovesicle(by adjusting the molar ratio of DOTAP/cholesterol-mi RNAs to 4:1)to carry mi R-29 a-3 p and mimic the exosomes.This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo,thus alleviating the establishment of a pro-metastatic environment for circulating lung tumor cells.
基金This work was supported by a National Research Foundation of Korea(NRF)grant funded by the Korean Government(MSIT)(NRF-2016R1A5A1010148,NRF-2019R1A2C1003111).
文摘There are extensive studies on the applications of extracellular vesicles(EVs)produced in cell culture for therapeutic drug development.However,large quantities of EVs are needed for in vivo applications,which requires high production costs and time.Thus,the development of new EV sources is essential to facilitate their use.Accordingly,plant-derived exosome-like nanovesicles are an emerging alternative for culture-derived EVs.Until now,however,few studies have explored their biological functions and uses.Therefore,it is necessary to elucidate biological activities of plant-derived exosome-like nanovesicles and harness vesicles for biomedical applications.Herein,cabbage and red cabbage were used as nanovesicle sources owing to their easy cultivation.First,an efficient method for nanovesicle isolation from cabbage(Cabex)and red cabbage(Rabex)was developed.Furthermore,isolated nanovesicles were characterized,and their biological functions were assessed.Both Cabex and Rabex promoted mammalian cell proliferation and,interestingly,suppressed inflammation in immune cells and apoptosis in human keratinocytes and fibroblasts.Finally,therapeutic drugs were encapsulated in Cabex or Rabex and successfully delivered to human cells,demonstrating the potential of these vesicles as alternative drug delivery vehicles.Overall,the current results provide strong evidence for the wide application of Cabex and Rabex as novel therapeutic biomaterials.
基金financially supported by the National Basic Research Program of China (No. 2015CB755500)the Natural Science Foundation of Guangdong Province (No. 2014A030312018)Science and Technology Planning Project of Guangdong Province (No. 2016A020215088)
文摘Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death.Nanoparticle-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these challenges.In the present study,amphipathic block polymer of methoxyl poly(ethylene glycol)-poly(aspartyl(dibutylethylenediamine)-co-phenylalanine)(m PEG-P(Asp(DBA)-co-Phe))was synthesized and self-assembled into p H-responsive polymeric vesicle.The vesicle was utilized to co-deliver cancer-associated epidermal growth factor(EGFR)inhibitor of afatinib and DNA-damaging chemotherapeutic doxorubicin hydrochloride(DOX)for enhanced non-small-cell lung cancer(NSCLC)therapy.As evaluated in vitro,the p H-responsive design of nanovesicle resulted in a rapid release of encapsulated drugs into tumor cells and caused enhanced cell apoptosis.In addition,in vivo therapeutic studies were conducted and the results evidenced that the co-delevery of DOX and afatinib using p H-sensitive nanovector was a promising strategy for NSCLC treatment.
基金supported by the National Natural Science Foundation of China(NSFC)projects(Nos.81901905,81830060,and 82050410449)China Postdoctoral Science Foundation(No.2019M660989).
文摘Translation of exosome-based therapies to pharmaceutical use is hindered by difficulties in large-scale and cost-effective production of clinical-grade exosomes.The rational design of nanovesicles that mimic the functionalities and physicochemical properties of exosomes may circumvent these issues.In this study,membranes and secretome from efficacy-potentiated mesenchymal stem cells(MSCs)were developed into size-controllable nanovesicles(Meseomes).MSCs were primed with interferon-y(IFNy)and tumor necrosis factor-a(TNFa),harvested,and exosome-mimicking Meseomes were subsequently synthesized via one-step extrusion.Meseomes demonstrated significant enhancement of pro-angiogenic,pro-proliferative,antiinflammatory,and anti-fibrotic effects on endothelial cells,macrophages,and hepatic stellate cells in vitro.Meseomes from primed MSCs benefited from an enrichment of bioactive and therapeutic molecules compared to nanovesicles from unprimed MSCs,as validated by liquid chromatography-mass spectrometry(LC-MS)proteomic analysis.Systemic administration of Meseomes to acute liver injury models resulted in the recovery of liver function,attenuated tissue necrosis.Further assessment of locally administered Meseomes in acute hindlimb ischemia models resulted in the salvage of the majority of the ischemic hindlimb(>80%),which was due to enhanced angiogenesis and M2 macrophage polarization.The versatility and therapeutic efficacy of our developed acellular Meseomes offer an appealing alternative to traditional cell or exosome therapies for regenerative and translational medicine.
基金financially supported by the National Key Research and Development Program of China (No.2021YFA1201200)the National Natural Science Foundation of China (Nos. 51833008, 52173141 and 82102192)+1 种基金Zhejiang Provincial Key Research and Development Program (No.2020C01123)China Postdoctoral Science Foundation (No.2019M662059)
文摘Oligonucleotide therapeutics have great potential to target the currently undruggable genes and to generate entirely new therapeutic paradigms in multiple types of disease,thus having attracted much attention in recent years.However,their applications are greatly hindered by a lack of safe and efficient oligonucleotide-delivery vectors.Polyplex nanovesicles formed from oligonucleotides and the cationic block have shown exceptional features for the delivery of therapeutic oligonucleotides and other biopharmaceuticals.Nevertheless,these polyplex nanovesicles are deeply fraught with difficulty in tolerating physiological ionic strength.Inspired by the high binding ability between the dipicolylamine(DPA)/zinc(Ⅱ)complex and the phosphodiester moieties of oligonucleotides,herein,we designed a coordinative cationic block to solve the intrinsic stability dilemma.Moreover,we found the stability of the resulted polyplex nanovesicles could be easily tuned by the content of coordinated zinc ions.In vitro cellular studies implied that the prepared zinc(Ⅱ)-coordinative polyplex nanovesicles preferred to retain in the lysosomes upon internalization,making them ideal delivery candidates for the lysosome-targeting oligonucleotide therapeutics.
基金financially supported by the National Natural Science Foundation of China (Nos.31771036,51703132)the Basic Research Program of Shenzhen (Nos.JCYJ20180507182413022,JCYJ20170412111100742)the Guangdong Province Natural Science Foundation of Major Basic Research and Cultivation Project (No.2018B030308003)。
文摘Gold nanovesicles(GVs) with unique plasmonic property and large cavity hold great potential as a stimuli-responsive nanocarrier to deliver drugs for efficient tumor chemotherapy and other therapies synergistically.Herein,we developed doxorubicin-loaded gold nanovesicles(DGVs),offering infrared thermal(IRT) and photoacoustic(PA) dual-modal imaging guided mild hype rthermia-enhanced chemophotothermal cancer synergistic therapy.The DGVs are self-assembled by gold nanoparticles modified with amphiphilic copolymer in a predetermined concentration of doxorubicin through film rehydration method.Under the influence of laser excitation,the as-prepared DGVs exhibited good photothermal effect,which triggered the structural disruption of GVs and thus,allowed the efficient release of encapsulated DOX to enhance cell uptake for fluorescence imaging and tumor chemotherapy,respectively.In addition,DGVs also showed a strong PA and IRT signals in vivo.Our study demonstrated the potential of DGVs as stimuli-responsive drug delivery systems and cancer theranostics.
基金supported by the NIH awards(Nos.U01DA056242,R01DK133864,and DP2AI160242).
文摘Extracellular vesicles are nano-to micro-scale,membrane-bound particles released by cells into extracellular space,and act as carriers of biomarkers and therapeutics,holding promising potential in translational medicine.However,the challenges remain in handling and detecting extracellular vesicles for disease diagnosis as well as exploring their therapeutic capability for disease treatment.Here,we review the recent engineering and technology advances by leveraging the power of sound waves to address the challenges in diagnostic and therapeutic applications of extracellular vesicles and biomimetic nanovesicles.We first introduce the fundamental principles of sound waves for understanding different acoustic-assisted extracellular vesicle technologies.We discuss the acoustic-assisted diagnostic methods including the purification,manipulation,biosensing,and bioimaging of extracellular vesicles.Then,we summarize the recent advances in acoustically enhanced therapeutics using extracellular vesicles and biomimetic nanovesicles.Finally,we provide perspectives into current challenges and future clinical applications of the promising extracellular vesicles and biomimetic nanovesicles powered by sound.
